Osmotic delivery systems for the oral administration of drugs are well known in the art. These systems dispense the active agent in a controlled and continuous manner over a prolonged period of time to produce a desired beneficial result. Such systems are typically represented by U.S. Pat. No. 3,845,770, U.S. Pat. No. 3,916,899, U.S. Pat. No. 4,016,880 and the like.
Characteristically, such systems employ a semi-permeable shaped wall membrane capable of imbibing gastrointestinal fluid, a core compartment containing the active agent, alone or together with pharmaceutically acceptable excipients, such as binders, osmotically active driving solutes, and tabletting excipients or combinations thereof, and at least one passageway in the wall, for dispensing the active agent, in communication with the core compartment and the external environment. In the gastrointestinal tract, the device imbibes fluid through the semi-permeable membrane which fluid dissolves the active agent or the osmotically active solute, or both, to form a solution or suspension which exhibits an osmotic pressure gradient against the wall membrane. As the wall membrane is substantially impermeable to the osmotically active solution or suspension, the solution or suspension, containing the drug, passes through the passageway, or passageways in the wall to the external environment upon activation. In general, useful wall materials and device parameters for such systems are described in U.S. Pat. No. 3,916,899, the disclosure of which is incorporated by reference herein, in toto.
Unfortunately many solid pharmaceutically acceptable active agents and conventional osmotically active driving solutes possess little or no inherent binding capabilities to semipermeable membrane films. Accordingly, attempts to film coat compressed core tablets, or the like, consisting of such agents, or admixtures of such agents and driving solutes, may result in poor adhesion between the core and the semipermeable membrane. As a consequence, the semipermeable membrane coat tends to peel off the core. This problem may be aggravated when attempts are made to coat such core tablets with a semipermeable film-forming solution using conventional air suspension techniques, such as the Wurster Air suspension technique, where the core tablet may pick up a static charge, further reducing uniform adhesion between the core and resultant membrane film.
Even when relatively high amounts of conventional polymeric binders, such as poly-N-vinylpyrrolidone, poly-C.sub.2 -C.sub.3 alkylene glycols, or hydroxy-lower alkylcellulose or mixtures thereof are uniformly distributed in the core composition as pharmaceutically acceptable tabletting excipients, poor adhesion between the core and membrane coating, resulting in delamination or membrane peeling, may be characteristically observed.
Also, the use of excessive amounts of conventional polymeric binders is generally undesirable where the unit dosage amount desired for the particular pharmaceutically acceptable active agent employed is sufficiently great that the cores employing such large amounts of binder exceeds the size for convenient oral unit dose administration to the warm blooded mammalian host. Moreover, excessive amounts of conventional polymeric binders can interfere with the desired continuous release profile of the active agent in the core by excessively retarding the dissolution and release of the active agent in the gastrointestinal tract or by clogging the one or more passageways, thereby occasioning potential rupturing of the device.
Surprisingly and unexpectedly, it has now been discovered that the active agent containing core may be substantially evenly coated with a thin discrete layer of a water-soluble, or water-dispersible, and water permeable substantially non-osmotically active solid polymeric binder, which treated core can thereafter be coated with semi-permeable membrane material which adhesively binds to the binding layer, to form a stable laminated osmotically activated device substantially free from the aforementioned defects.